Abrahamsson Annelie, Rzepecka Anna, Romu Thobias, Borga Magnus, Leinhard Olof Dahlqvist, Lundberg Peter, Kihlberg Johan, Dabrosin Charlotta
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University , Linköping, Sweden.
Department of Radiology and Department of Medical and Health Sciences, Linköping University , Linköping, Sweden.
Oncoimmunology. 2016 Sep 2;5(10):e1229723. doi: 10.1080/2162402X.2016.1229723. eCollection 2016.
Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment. Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1β was decreased in dense breasts. No differences were found in levels of IL-1β, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue. Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.
炎症是致癌作用的标志之一。乳腺钼靶密度高与乳腺癌风险增加有关，但其背后的机制尚不清楚。我们评估了不同乳腺钼靶密度的乳房在炎症微环境中是否存在差异。参加乳腺钼靶筛查项目的绝经后女性在其常规钼靶片上被评估为极度致密乳房（n = 20）或完全脂肪型乳房（非致密型，n = 19）。此后，邀请这些女性进行磁共振成像（MRI）、用于收集细胞外分子的微透析以及用于研究目的的核心组织活检。在MRI上，计算瘦组织分数（LTF）以连续测量乳腺密度。LTF证实了从钼靶片中的选择，并提供了乳腺密度的连续测量值。微透析显示，与非致密型乳房相比，致密型乳腺组织中细胞外白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、血管内皮生长因子和趋化因子配体5（CCL5）水平显著升高。此外，致密型乳房中白细胞介素-1受体拮抗剂（IL-1Ra）与白细胞介素-1β（IL-1β）的比值降低。两种乳腺组织类型之间在IL-1β、IL-1Ra、CCL2、瘦素、脂联素或瘦素与脂联素的比值水平上未发现差异。检测到LTF与促炎细胞因子之间以及细胞因子之间存在显著正相关。核心活检的染色显示致密型乳腺组织中免疫细胞水平升高。我们的数据表明，绝经后女性的致密型乳腺组织与促炎微环境有关，如果在更大的队列中得到证实，则为致密型乳腺组织女性的预防治疗提供了新的靶点。
